This invention relates to medicinal compositions of matter. More particularly, it relates to medicinal compositions of matter which comprise an estrogenic compound in combination with a cruciferous indole compound, including without limitation indole 3-carbinol, diindolylmethane, and including any derivatives of the foregoing. Compositions according to the invention are suitable for administration orally, or by any other conventional means of administration.
Estrogen replacement therapy (ERT) is a commonly-used therapeutic strategy in symptoms associated with menopause and perimenopause, in addition to its use in preventing osteoporosis and other degenerative conditions associated with ovarian failure, or relatively low estrogen levels resulting from other causes. ERT is often associated with certain side effects, and a slight increase in the risk of certain types of breast cancer are recognized with its long-term use. Because of both the side effects and the fear of breast cancer, compliance with ERT by patients is notoriously poor. Many different types of estrogen, different doses, and different forms of administration have been developed to help enhance compliance with ERT. Unfortunately none of the existing ERT products adequately address patient concerns of side effects and increased risk of breast cancer. From metabolic pathway and studies in carcinoma, it has been determined that a preponderance of 16-hydroxyestrogen metabolites is generally associated with an increased risk for breast cancer, and that a preponderance of 2-hydroxyestrogen metabolites is generally associated with a decreased risk of breast cancer. Thus, if a material were available which could provide the beneficial effects of the presence of an estrogenic substance in a body having reduced capability to produce its own estrogens while reducing the quantity of 16-hydroxyestrogen metabolites and simultaneously increasing the quantity of 2-hydroxyestrogen metabolites in the patient""s bloodstream, such a material and methods for its administration would be a valuable therapeutic aid for improving many patients"" quality of life.
A particular class of compounds known as cruciferous indole compounds are known to exist in a wide variety of plant and particularly vegetable matter. These compounds have been shown to alter steroid hormone metabolism in the human organism. In U.S. Pat. No. 5,948,808 methods for treatment of breast cancer are described using indole-3-carbinol, diindolylmethane, and substituted analogs thereof in the capacity of anti-estrogens. U.S. Pat. No. 6,001,868 discloses a method of inhibiting tumor cell growth comprising contacting a target tumor cell with, or administering to an individual in need thereof, an effective amount of an indole-3-carbinol compound or a derivative thereof, wherein said compound is stable in acidic aqueous solution. However, the inhibition is described therein as being limited to estrogen-independent and the xe2x80x9cindole-3-carbinol compoundxe2x80x9d is not indole-3-carbinol, 3,3xe2x80x2-diindolylmethane.
The present invention is concerned with medicinal compositions useful for estrogen replacement therapy (ERT) of perimenopause, menopause, or any other cause of ovarian failure or condition in which the production of the body""s natural hormones are reduced or eliminated. Compositions according to the invention comprise an estrogenic substance component which may include without limitation estrogen; conjugated estrogens; dienestrol; estrone; esterified estrogens; estradiol; estriol; and estropipate; ethinyl estradiol
The cruciferous indole component may include without limitation indole 3-carbinol, diindolylmethane, or any derivative of the foregoing, such as 5-methyl-indole-3-carbinol, 5-ethyl-indole-3-carbinol, 5-propyl-indole-3-carbinol, 5-butyl-indole-3-carbinol, 5-pentyl-indole-3-carbinol, 5-methoxy-indole-3-carbinol, 5-ethoxy-indole-3-carbinol, 5-propyloxy-indole-3-carbinol, 5-butyloxy-indole-3-carbinol, 5-amyloxy-indole-3-carbinol, N-methyl-indole-3-carbinol, N-ethyl-indole-3-carbinol, N-propyl-indole-3-carbinol, N-butyl-indole-3-carbinol, N-pentyl-indole-3-carbinol, 2-methyl-indole-3-carbinol, 2-ethyl-indole-3-carbinol, 2-propyl-indole-3-carbinol, 2-butyl-indole-3-carbinol and 2-pentyl-indole-3-carbinol.
The invention is also concerned with a process for treating a human patient who is afflicted with menopause, perimenopause, or any other cause of ovarian failure or reduced hormone levels, which comprises the steps of providing a composition according to the invention and introducing such a composition into such patient""s body.